METABOLISM-BASED DRUG SCREENING PLATFORM IN BIOENGINEERED ZEBRAFISH

摘要

The present application provides a novel drug screening platform designed to identify drugs that favorably modulate cellular bioenergetics in the human brain of a zebrafish which has been modified by altering a teleost gene that corresponds to a human gene associated with a brain dysfunction disorder (such as epilepsy). The drug screening platform are also useful for determining a mutation in a human gene associated with a brain dysfunction disorder that is associated with a human individual responsive to the treatment of a compound. Also provided are modified teleosts useful for the methods described herein.

主权项

1. A method of identifying a compound that modulates mitochondrial function in the human brain using a modified teleost, wherein the modified teleost comprises a teleost gene that corresponds to a human gene associated with a brain dysfunction disorder, wherein said teleost gene is modified as compared to that of a wildtype teleost, the method comprising:
a) contacting the modified teleost with a compound, b) assaying for mitochondrial function in the modified teleost, wherein a modulated mitochondrial function in the modified teleost compared to a control teleost not contacted with the compound is indicative of a compound that modulates mitochondrial function in the human brain.